Project Summary Candidate Kimberly G. Blumenthal, MD is an Assistant in Medicine in the Allergy and Clinical Immunology Unit at Massachusetts General Hospital (MGH) and an Instructor of Medicine at Harvard Medical School (HMS). After her undergraduate training in economics at Columbia University and the London School of Economics, she received her M.D. from Yale University. Dr. Blumenthal began working with Rochelle P. Walensky, MD, MPH and the Medical Practice Evaluation Center (MPEC) at MGH after completion of her clinical training at MGH in Internal Medicine and Allergy/Immunology. Dr. Blumenthal studies drug allergy epidemiology and impact on patient care; she has authored 13 total manuscripts, with 7 first-authored peer-reviewed manuscripts, including publications in the Journal of Allergy and Clinical Immunology and Clinical Infectious Diseases. Dr. Blumenthal is completing a Masters of Science in Epidemiology at the Harvard T.H. Chan School of Public Health. Dr. Blumenthal's goal is to become a national leader in drug allergy with methods expertise in clinical epidemiology and decision science. Mentorship, Training Activities, and Environment Dr. Blumenthal will perform the work outlined in this proposal at MGH under the mentorship of Rochelle P. Walensky, MD, MPH and co-mentorship of Aleena Banerji, MD. Dr. Walensky, Co-director of MPEC, is a nationally-recognized expert in decision science whose research has motivated national and international policies related to testing and treatment of Human Immunodeficiency Virus. Dr. Walensky has been NIH-funded since 2006; she has served as a mentor to over 5 prior K awardees, and has successfully transitioned fellows to independent R01-funded research careers. Dr. Banerji is a nationally-recognized expert in drug allergy with expertise in epidemiology and outcomes research. Dr. Blumenthal's research will benefit from the specific expertise of collaborators: Carlos A. Camargo, MD, DrPH (epidemiology), Robert A. Parker, ScD (biostatistics), Stephen Resch, PhD (resource utilization), Li Zhou, MD, PhD (bioinformatics) and Erica S. Shenoy, MD, PhD (infection control). Dr. Blumenthal has organized a Scientific Advisory Board, chaired by Dr. Camargo, that includes: Andrew D. Luster, MD, PhD, Katrina A. Armstrong, MD, MSCE and David W. Bates, MD, MSc. To complement the expertise of her mentors, collaborators and advisors, Dr. Blumenthal will complete didactic courses to acquire new research skills, including linkage and analysis of large databases, resource utilization analysis and simulation modeling and cost-effectiveness analysis. The collaborative opportunities, intellectual environment, and resources available to Dr. Blumenthal are outstanding and will provide her with a clear path to independent research success. Research Penicillin (PCN) allergy is reported by over 10% of the U.S. population, though a self-reported PCN allergy infrequently reflects an actual inability to tolerate PCNs and other ?-lactam antibiotics (e.g., cephalosporins). Unnecessary use of ?-lactam alternative antibiotics may lead to more antimicrobial resistance and healthcare-associated infections, as well as higher costs. Although the prevalence of self-reported PCN allergy does not equate with true PCN hypersensitivity, PCNs and other ?-lactam antibiotics are the most common cause of drug hypersensitivity reactions, the immune-mediated subset of adverse drug reactions (ADRs). ADRs have a large impact on patient morbidity, mortality and cost of care. PCN allergy evaluation with skin testing can distinguish between patients with and without true PCN hypersensitivity. Implementation of a history-appropriate PCN skin testing may improve clinical outcomes and the efficiency of resource use. The K01 scientific program, The Clinical and Economic Impact of Penicillin Allergy, has three specific aims that lie at the research intersection of Allergy/Immunology, Infectious Diseases and healthcare policy, and align with national priorities including curbing antimicrobial resistance and improving healthcare quality and safety: 1) To assess the clinical and economic impact of reported PCN allergy in a large U.S. healthcare system using a large patient cohort combined from separate internal databases. 2) To determine the frequency, predictors and healthcare resource impact of PCN and cephalosporin hypersensitivity reactions in the outpatient setting using an internal cohort of patients prescribed PCNs or cephalosporins over a 10-year period. 3) To project the clinical outcomes, budgetary impact and cost-effectiveness of implementing a PCN skin testing program in the U.S. using a simulation model. Completion of this research proposal and training plan will position Dr. Blumenthal for an independent research career as a drug allergy expert with methods skills in clinical epidemiology and decision science.